The evolving landscape of Alzheimer's disease (AD) research is witnessing a significant shift towards decentralized clinical trials (DCTs) to enhance accessibility and improve patient participation. These trials aim to balance the collection of comprehensive data with the unique needs of a patient population experiencing cognitive decline.
Decentralized Approach in Action
Eli Lilly's ongoing phase 3 TRAILBLAZER-ALZ 3 trial (NCT05026866) exemplifies this approach. The trial assesses the efficacy of donanemab (Kisunla) in preclinical AD using a DCT model that includes mobile research units, community screenings, and remote cognitive assessments via electronic tablets provided to participants and their study partners. According to Jessica Langbaum, PhD, senior director of research strategy at Banner Alzheimer’s Institute, this decentralized model addresses key logistical barriers faced by underrepresented populations in accessing AD clinical trials.
Challenges and Opportunities
While therapies like donanemab and lecanemab (Leqembi) offer renewed hope, they face regulatory and access challenges. The European Medicines Agency (EMA) noted that Leqembi’s efficacy was “not large enough” to outweigh its safety risks. Similarly, the UK’s National Institute for Health and Care Excellence (NICE) recommended against the widespread use of Kisunla.
Sandi See Tai, chief development officer at Lexeo Therapeutics, emphasizes the importance of convenience for both patients and caregivers when designing AD trials. Lexeo’s AAVrh10-based gene therapy LX1001, requires a one-time dose followed by five years of follow-up, necessitating strategies to maintain patient engagement. Virtual visits and logistical support for blood sampling are offered to reduce the need for travel. However, procedures like MRIs, PET scans, and lumbar punctures still require in-person visits to ensure data integrity.
The Role of Digital Health Technologies
The integration of digital health technologies, such as wearables and sensors, offers opportunities to continuously measure health metrics like physical activity, sleep, cognition, mood, and speech. Sarah Lott, research lead at the Digital Medicine Society (DiME), highlights the potential of these tools to provide a more comprehensive and dynamic picture of a patient’s health over time and democratize access to clinical trials by enabling remote monitoring.
Telemedicine is the leading virtual tool used in Alzheimer’s DCTs, utilized in 55.7% of all such trials. Shobha Dhadda, Eisai’s chief clinical science & operations officer, notes that Eisai leverages telemedicine and wearable devices for real-time monitoring of cognitive function and patient safety. Digital cognitive testing platforms allow for standardized assessment, while remote consultations reduce the need for frequent on-site visits.
Addressing Data Integrity and Patient Needs
Despite the benefits, challenges remain in ensuring data integrity, addressing technology literacy among older populations, and tailoring digital tools to meet patient needs. Lott emphasizes the importance of user-friendly technology and suggests the use of ambient technologies, such as cameras and pressure mats, to collect data without burdening the patient.
Eisai prioritizes Quality of Life (QoL) metrics to ensure a holistic understanding of treatment impact. Dhadda explains that the inclusion of wearables and digital platforms in trials provides dynamic QoL insights, facilitating a more comprehensive assessment of therapies’ effectiveness from both medical and patient perspectives.
